Stage-specific differences in secretory profile of mesenchymal stromal cells (MSCs) subjected to early- vs late-stage OA synovial fluid.

Autor: Gómez-Aristizábal A; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; The Arthritis Program, Toronto Western Hospital, Toronto, ON, Canada., Sharma A; The Arthritis Program, Toronto Western Hospital, Toronto, ON, Canada; Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada., Bakooshli MA; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, ON, Canada., Kapoor M; The Arthritis Program, Toronto Western Hospital, Toronto, ON, Canada; Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada., Gilbert PM; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, ON, Canada; Department of Biochemistry, University of Toronto, ON, Canada., Viswanathan S; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada; The Arthritis Program, Toronto Western Hospital, Toronto, ON, Canada; Division of Genetics and Development, Krembil Research Institute, Toronto, ON, Canada; Cell Therapy Program, University Health Network, Toronto, Canada. Electronic address: sowmya.viswanathan@uhnresearch.ca., Gandhi R; The Arthritis Program, Toronto Western Hospital, Toronto, ON, Canada; Division of Orthopaedic Surgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada. Electronic address: rajiv.gandhi@uhn.ca.
Jazyk: angličtina
Zdroj: Osteoarthritis and cartilage [Osteoarthritis Cartilage] 2017 May; Vol. 25 (5), pp. 737-741. Date of Electronic Publication: 2016 Nov 25.
DOI: 10.1016/j.joca.2016.11.010
Abstrakt: Objective: Although, mesenchymal stromal cells (MSCs) are being clinically investigated for their use in osteoarthritis (OA), it is unclear whether their postulated therapeutic properties are equally effective in the early- and late-stages of OA. In this study we investigated MSC cytokine secretion post-exposure to synovial fluid (SF), obtained from early- vs late-stage knee OA patients to justify a potential patient stratification strategy to maximize MSC-mediated treatment effects.
Method: Subjects were recruited and categorized into early- [Kellgren-Lawrence (KL) grade I/II, n = 12] and late-stage (KL-III/IV, n = 12) knee OA groups. SF samples were obtained, and their proteome was tested using multiplex assays, after 3-days culture, with and without MSCs. SFs cultured without MSCs were used as a baseline to identify MSC-secreted factors into SFs cultured with MSCs. Linear mixed-effect models and non-parametric tests were used to identify alterations in the MSC secretome during exposure to OA SF (3-days). MSCs cultured for 3-days in 0.5% fetal bovine serum (FBS)-supplemented medium were used to compare SF results with culture medium.
Results: Following exposure to OA SF, the MSC secretome contained proteins that are involved in tissue repair, angiogenesis, chemotaxis, matrix remodeling and the clotting process. However, chemokine (C-X-C motif) ligand-8 (CXCL8; chemoattractant), interleukin-6 (IL6) and chemokine (C-C motif) ligand 2 (CCL2) were elevated in the MSC-secretome in response to early- vs late-stage OA SF.
Conclusion: Early- vs late-stage OA SF samples elicit a differential MSC secretome response, arguing for stratification of OA patients to maximize MSC-mediated therapeutic effects.
(Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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